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SPHK1 Antibody (N-term P74)

Purified Rabbit Polyclonal Antibody (Pab)

     
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  • IHC-P - SPHK1 Antibody (N-term P74) AP7237d
    Immunohistochemical analysis of paraffin-embedded H. kidney section using SPHK1 Antibody(N-term P74) (Cat#AP7237d). AP7237d was diluted at 1:100 dilution. A peroxidase-conjugated goat anti-rabbit IgG at 1:400 dilution was used as the secondary antibody, followed by DAB staining.
  • IHC-P - SPHK1 Antibody (N-term P74) AP7237d
    Immunohistochemical analysis of paraffin-embedded M. kidney section using SPHK1 Antibody(N-term P74) (Cat#AP7237d). AP7237d was diluted at 1:100 dilution. A peroxidase-conjugated goat anti-rabbit IgG at 1:400 dilution was used as the secondary antibody, followed by DAB staining.
  • WB - SPHK1 Antibody (N-term P74) AP7237d
    Western blot analysis of lysates from HepG2 cell line and human heart, skeletal muscle, kidney tissue lysate(from left to right), using SPHK1 Antibody (N-term P74)(Cat. #AP7237d). AP7237d was diluted at 1:1000 at each lane. A goat anti-rabbit IgG H&L(HRP) at 1:5000 dilution was used as the secondary antibody. Lysates at 35ug per lane.
  • SPECIFICATION
  • CITATIONS: 2
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  • BACKGROUND
Product Information
Application
  • Applications Legend:
  • WB=Western Blot
  • IHC=Immunohistochemistry
  • IHC-P=Immunohistochemistry (Paraffin-embedded Sections)
  • IHC-F=Immunohistochemistry (Frozen Sections)
  • IF=Immunofluorescence
  • FC=Flow Cytopmetry
  • IC=Immunochemistry
  • ICC=Immunocytochemistry
  • E=ELISA
  • IP=Immunoprecipitation
  • DB=Dot Blot
  • CHIP=Chromatin Immunoprecipitation
  • FA=Fluorescence Assay
  • IEM=Immunoelectronmicroscopy
  • EIA=Enzyme Immunoassay
IHC-P, WB, E
Primary Accession Q9NYA1
Reactivity Human
Host Rabbit
Clonality Polyclonal
Isotype Rabbit Ig
Antigen Region 59-89 aa
Additional Information
Other Names Sphingosine kinase 1, SK 1, SPK 1, SPHK1, SPHK, SPK
Target/Specificity This SPHK1 antibody is generated from rabbits immunized with a KLH conjugated synthetic peptide between 59-89 amino acids from the N-terminal region of human SPHK1.
Dilution IHC-P~~1:100
WB~~1:1000
Format Purified polyclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is prepared by Saturated Ammonium Sulfate (SAS) precipitation followed by dialysis against PBS.
StorageMaintain refrigerated at 2-8°C for up to 2 weeks. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.
PrecautionsSPHK1 Antibody (N-term P74) is for research use only and not for use in diagnostic or therapeutic procedures.
Protein Information
Name SPHK1 (HGNC:11240)
Function Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (PubMed:20577214, PubMed:23602659, PubMed:29662056, PubMed:24929359, PubMed:11923095). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF- kappa-B in response to TNF signaling leading to IL17 secretion (PubMed:20577214). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096). Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (PubMed:28049734, PubMed:24929359). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698).
Cellular Location Cytoplasm. Nucleus. Cell membrane. Endosome membrane; Peripheral membrane protein. Membrane, clathrin-coated pit. Cell junction, synapse {ECO:0000250|UniProtKB:Q8CI15}. Note=Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner (PubMed:19854831). Binds to membranes containing negatively charged lipids but not neutral lipids (PubMed:24929359). Recruited to endocytic membranes by sphingosine where promotes membrane fusion (By similarity) {ECO:0000250|UniProtKB:Q8CI15, ECO:0000269|PubMed:19854831, ECO:0000269|PubMed:24929359}
Tissue Location Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Expressed in brain cortex (at protein level) (PubMed:29662056). EMBL; AF266756; AAF73470.1; -; mRNA EMBL; AF238083; AAF73423.1; -; mRNA EMBL; AF200328; AAG01980.1; -; mRNA EMBL; AK023393; BAB14558.1; -; mRNA EMBL; AK292294; BAF84983.1; -; mRNA EMBL; AK022402; BAB14028.1; -; mRNA EMBL; AJ245504; CAB92131.1; -; mRNA EMBL; AC090699; -; NOT_ANNOTATED_CDS; Genomic_DNA EMBL; CH471099; EAW89392.1; -; Genomic_DNA EMBL; CH471099; EAW89393.1; -; Genomic_DNA EMBL; BC009419; AAH09419.1; -; mRNA EMBL; BC014439; AAH14439.1; -; mRNA EMBL; BC030553; AAH30553.1; -; mRNA CCDS; CCDS11744.1; -. [Q9NYA1-2] CCDS; CCDS45785.1; -. [Q9NYA1-1] CCDS; CCDS59297.1; -. [Q9NYA1-3] RefSeq; NP_001136073.1; NM_001142601.1. [Q9NYA1-1] RefSeq; NP_001136074.1; NM_001142602.1. [Q9NYA1-1] RefSeq; NP_068807.2; NM_021972.3. [Q9NYA1-3] RefSeq; NP_892010.2; NM_182965.2. [Q9NYA1-2] RefSeq; XP_005257823.1; XM_005257766.2 PDB; 3VZB; X-ray; 2.00 A; A/B/C=9-364 PDB; 3VZC; X-ray; 2.30 A; A/B/C/D/E/F=9-364 PDB; 3VZD; X-ray; 2.30 A; A/B/C/D/E/F=9-364 PDB; 4L02; X-ray; 2.75 A; A/B/C=9-364 PDB; 4V24; X-ray; 1.80 A; A/B=1-363 PDBsum; 3VZB; - PDBsum; 3VZC; - PDBsum; 3VZD; - PDBsum; 4L02; - PDBsum; 4V24; - SMR; Q9NYA1; - BioGrid; 114396; 18 IntAct; Q9NYA1; 58 MINT; Q9NYA1; - STRING; 9606.ENSP00000313681; - BindingDB; Q9NYA1; - ChEMBL; CHEMBL4394; - DrugBank; DB08868; Fingolimod GuidetoPHARMACOLOGY; 2204; - SwissLipids; SLP:000000111; - iPTMnet; Q9NYA1; - PhosphoSitePlus; Q9NYA1; - BioMuta; SPHK1; - DMDM; 17369329; - jPOST; Q9NYA1; - MassIVE; Q9NYA1; - MaxQB; Q9NYA1; - PaxDb; Q9NYA1; - PeptideAtlas; Q9NYA1; - PRIDE; Q9NYA1; - ProteomicsDB; 83202; -. [Q9NYA1-1] ProteomicsDB; 83203; -. [Q9NYA1-2] Antibodypedia; 19687; 700 antibodies DNASU; 8877; - Ensembl; ENST00000323374; ENSP00000313681; ENSG00000176170. [Q9NYA1-2] Ensembl; ENST00000392496; ENSP00000376285; ENSG00000176170. [Q9NYA1-1] Ensembl; ENST00000545180; ENSP00000440970; ENSG00000176170. [Q9NYA1-1] Ensembl; ENST00000590959; ENSP00000468547; ENSG00000176170. [Q9NYA1-3] Ensembl; ENST00000592299; ENSP00000465726; ENSG00000176170. [Q9NYA1-1] GeneID; 8877; - KEGG; hsa:8877; - UCSC; uc002jrf.1; human. [Q9NYA1-1] CTD; 8877; - DisGeNET; 8877; - GeneCards; SPHK1; - HGNC; HGNC:11240; SPHK1 HPA; ENSG00000176170; Low tissue specificity MIM; 603730; gene neXtProt; NX_Q9NYA1; - OpenTargets; ENSG00000176170; - PharmGKB; PA36070; - eggNOG; KOG1116; Eukaryota eggNOG; COG1597; LUCA GeneTree; ENSGT00940000157864; - HOGENOM; CLU_013399_1_0_1; - InParanoid; Q9NYA1; - KO; K04718; - OMA; GNMAIMS; - OrthoDB; 681139at2759; - PhylomeDB; Q9NYA1; - TreeFam; TF354296; - BRENDA; 2.7.1.91; 2681 Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling SABIO-RK; Q9NYA1; - SignaLink; Q9NYA1; - SIGNOR; Q9NYA1; - ChiTaRS; SPHK1; human GeneWiki; Sphingosine_kinase_1; - GenomeRNAi; 8877; - Pharos; Q9NYA1; Tchem PRO; PR:Q9NYA1; - Proteomes; UP000005640; Chromosome 17 RNAct; Q9NYA1; protein Bgee; ENSG00000176170; Expressed in tibial nerve and 152 other tissues ExpressionAtlas; Q9NYA1; baseline and differential Genevisible; Q9NYA1; HS GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB GO; GO:0005737; C:cytoplasm; IDA:UniProtKB GO; GO:0005829; C:cytosol; IDA:HPA GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB GO; GO:0005634; C:nucleus; ISS:UniProtKB GO; GO:0005886; C:plasma membrane; IDA:UniProtKB GO; GO:0098793; C:presynapse; ISS:UniProtKB GO; GO:0016407; F:acetyltransferase activity; ISS:UniProtKB GO; GO:0005524; F:ATP binding; IDA:UniProtKB GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB GO; GO:0017050; F:D-erythro-sphingosine kinase activity; IDA:UniProtKB GO; GO:0003677; F:DNA binding; IDA:MGI GO; GO:0008289; F:lipid binding; IDA:UniProtKB GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro GO; GO:0051721; F:protein phosphatase 2A binding; IPI:BHF-UCL GO; GO:0008481; F:sphinganine kinase activity; IDA:UniProtKB GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; IMP:UniProtKB GO; GO:0001568; P:blood vessel development; IEA:Ensembl GO; GO:0007420; P:brain development; IEA:Ensembl GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB GO; GO:0071897; P:DNA biosynthetic process; IEA:Ensembl GO; GO:0006954; P:inflammatory response; IEA:Ensembl GO; GO:0035556; P:intracellular signal transduction; TAS:UniProtKB GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI GO; GO:1900060; P:negative regulation of ceramide biosynthetic process; IDA:UniProtKB GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:MGI GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB GO; GO:0045931; P:positive regulation of mitotic cell cycle; IDA:UniProtKB GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:UniProtKB GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:UniProtKB GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB GO; GO:0045987; P:positive regulation of smooth muscle contraction; IDA:UniProtKB GO; GO:0006473; P:protein acetylation; ISS:UniProtKB GO; GO:0006457; P:protein folding; TAS:Reactome GO; GO:0030100; P:regulation of endocytosis; IDA:UniProtKB GO; GO:1905364; P:regulation of endosomal vesicle fusion; ISS:UniProtKB GO; GO:0032651; P:regulation of interleukin-1 beta production; IEA:Ensembl GO; GO:1903978; P:regulation of microglial cell activation; ISS:UniProtKB GO; GO:0150077; P:regulation of neuroinflammatory response; ISS:UniProtKB GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB GO; GO:0034612; P:response to tumor necrosis factor; IDA:UniProtKB GO; GO:0046521; P:sphingoid catabolic process; NAS:UniProtKB GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome GO; GO:0046512; P:sphingosine biosynthetic process; IMP:UniProtKB GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB Gene3D; 3.40.50.10330; -; 1 InterPro; IPR017438; ATP-NAD_kinase_N InterPro; IPR001206; Diacylglycerol_kinase_cat_dom InterPro; IPR016064; NAD/diacylglycerol_kinase_sf Pfam; PF00781; DAGK_cat; 1 SMART; SM00046; DAGKc; 1 SUPFAM; SSF111331; SSF111331; 1 PROSITE; PS50146; DAGK; 1 1: Evidence at protein level; 3D-structure; Alternative splicing; ATP-binding; Calmodulin-binding; Cell junction; Cell membrane; Coated pit; Cytoplasm; Endosome; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Synapse; Transferase CHAIN 1..384 /note="Sphingosine kinase 1" /id="PRO_0000181357" DOMAIN 12..159 /note="DAGKc" /evidence="ECO:0000255|PROSITE-ProRule:PRU00783" NP_BIND 22..24 /note="ATP" NP_BIND 54..58 /note="ATP" NP_BIND 111..113 /note="ATP" NP_BIND 341..343 /note="ATP" REGION 79..82 /note="Substrate binding" /evidence="ECO:0000269|PubMed:23602659" MOTIF 147..155 /note="Nuclear export signal 1" MOTIF 161..169 /note="Nuclear export signal 2" ACT_SITE 81 /note="Proton donor/acceptor" /evidence="ECO:0000269|PubMed:23602659" BINDING 86 /note="ATP" BINDING 178 /note="Substrate" BINDING 185 /note="ATP" BINDING 191 /note="ATP" MOD_RES 193 /note="Phosphothreonine" /evidence="ECO:0000244|PubMed:18669648" MOD_RES 225 /note="Phosphoserine" /evidence="ECO:0000269|PubMed:20577214" VAR_SEQ 1 /note="M -> MSAQVLGFLRSWTPLPLAAPRGPAAAGNDAGAPAATAPGGEGEPHSR PCDARLGSTDKELKAGAAATGSAPTAPGTPWQREPRVEVM (in isoform 2)" /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" /id="VSP_035453" VAR_SEQ 3 /note="P -> PVVGCGRGLFGFVFS (in isoform 3)" /evidence="ECO:0000303|PubMed:15489334" /id="VSP_047078" MUTAGEN 81 /note="D->A: Loss of enzyme activity." /evidence="ECO:0000269|PubMed:23602659" MUTAGEN 81 /note="D->N: Strongly reduced enzyme activity." /evidence="ECO:0000269|PubMed:23602659" MUTAGEN 82 /note="G->D: Loss of enzyme activity." /evidence="ECO:0000269|PubMed:20577214" MUTAGEN 194 /note="L->Q: Loss of binding to negatively charged membranes, diffuse cytosolic distribution." /evidence="ECO:0000269|PubMed:24929359" MUTAGEN 197..198 /note="FL->AQ: Loss of binding to negatively charged membranes, diffuse cytosolic distribution." /evidence="ECO:0000269|PubMed:24929359" MUTAGEN 197 /note="F->A: Abolishes interaction with CIB1; when associated with A-198." MUTAGEN 198 /note="L->A: Abolishes interaction with CIB1; when associated with A-197." CONFLICT 6 /note="Missing (in Ref. 4; CAB92131)" /evidence="ECO:0000305" CONFLICT 11..15 /note="LPRPC -> ARL (in Ref. 4; CAB92131)" /evidence="ECO:0000305" CONFLICT 114..115 /note="NA -> KP (in Ref. 4; CAB92131)" /evidence="ECO:0000305" CONFLICT 251 /note="V -> M (in Ref. 2; AAF73423)" /evidence="ECO:0000305" CONFLICT 260 /note="V -> I (in Ref. 2; AAF73423)" /evidence="ECO:0000305" CONFLICT 302 /note="L -> F (in Ref. 2; AAF73423)" /evidence="ECO:0000305" CONFLICT 325 /note="V -> G (in Ref. 4; CAB92131)" /evidence="ECO:0000305" CONFLICT 337 /note="V -> M (in Ref. 3; AAG01980)" /evidence="ECO:0000305" STRAND 13..21 /evidence="ECO:0000244|PDB:4V24" TURN 26..29 /evidence="ECO:0000244|PDB:4V24" HELIX 30..37 /evidence="ECO:0000244|PDB:4V24" HELIX 39..44 /evidence="ECO:0000244|PDB:4V24" STRAND 47..53 /evidence="ECO:0000244|PDB:4V24" HELIX 59..66 /evidence="ECO:0000244|PDB:4V24" HELIX 69..71 /evidence="ECO:0000244|PDB:3VZB" STRAND 73..80 /evidence="ECO:0000244|PDB:4V24" HELIX 81..92 /evidence="ECO:0000244|PDB:4V24" HELIX 97..100 /evidence="ECO:0000244|PDB:4V24" STRAND 105..109 /evidence="ECO:0000244|PDB:4V24" HELIX 115..123 /evidence="ECO:0000244|PDB:4V24" HELIX 131..144 /evidence="ECO:0000244|PDB:4V24" STRAND 146..157 /evidence="ECO:0000244|PDB:4V24" STRAND 162..172 /evidence="ECO:0000244|PDB:4V24" HELIX 173..181 /evidence="ECO:0000244|PDB:4V24" HELIX 182..190 /evidence="ECO:0000244|PDB:4V24" HELIX 191..201 /evidence="ECO:0000244|PDB:4V24" STRAND 206..214 /evidence="ECO:0000244|PDB:4V24" HELIX 215..218 /evidence="ECO:0000244|PDB:4V24" STRAND 230..232 /evidence="ECO:0000244|PDB:3VZB" STRAND 249..251 /evidence="ECO:0000244|PDB:4V24" STRAND 255..266 /evidence="ECO:0000244|PDB:4V24" STRAND 285..291 /evidence="ECO:0000244|PDB:4V24" HELIX 296..305 /evidence="ECO:0000244|PDB:4V24" HELIX 306..308 /evidence="ECO:0000244|PDB:4V24" HELIX 311..314 /evidence="ECO:0000244|PDB:4V24" STRAND 319..331 /evidence="ECO:0000244|PDB:4V24" STRAND 333..335 /evidence="ECO:0000244|PDB:4V24" STRAND 337..340 /evidence="ECO:0000244|PDB:4V24" STRAND 343..346 /evidence="ECO:0000244|PDB:4V24" STRAND 350..362 /evidence="ECO:0000244|PDB:4V24" VARIANT Q9NYA1-2:34 /note="A -> T (in dbSNP:rs346803)" /evidence="ECO:0000305" /id="VAR_082919" SEQUENCE 384 AA; 42518 MW; EB04A7F2034C2DB0 CRC64; MDPAGGPRGV LPRPCRVLVL LNPRGGKGKA LQLFRSHVQP LLAEAEISFT LMLTERRNHA RELVRSEELG RWDALVVMSG DGLMHEVVNG LMERPDWETA IQKPLCSLPA GSGNALAASL NHYAGYEQVT NEDLLTNCTL LLCRRLLSPM NLLSLHTASG LRLFSVLSLA WGFIADVDLE SEKYRRLGEM RFTLGTFLRL AALRTYRGRL AYLPVGRVGS KTPASPVVVQ QGPVDAHLVP LEEPVPSHWT VVPDEDFVLV LALLHSHLGS EMFAAPMGRC AAGVMHLFYV RAGVSRAMLL RLFLAMEKGR HMEYECPYLV YVPVVAFRLE PKDGKGVFAV DGELMVSEAV QGQVHPNYFW MVSGCVEPPP SWKPQQMPPP EEPL
Research Areas
Citations ( 0 )

Background

Sphingosine Kinase (SphK) catalyzes the phosphorylation of the lipid sphingosine, creating the bioactive lipid sphingosine-1-phosphate (S1P). S1P subsequently signals through cell surface G protein-coupled receptors, as well as intracellularly, to modulate cell proliferation, survival, motility and differentiation. SphK is an important signaling enzyme which is activated by diverse agents, including growth factors that signal through receptor tyrosine kinases, agents activating G protein-coupled receptors, and immunoglobulin receptors. Two SphK isotypes, SphK-1 and SphK-2, have been cloned, and both isotypes are ubiquitously expressed. SphK-1 has been shown to mediate cell growth, prevention of apoptosis, and cellular transformation, and is upregulated in a variety of human tumors. In contrast, SphK-2 increases apoptosis, and may be responsible for phosphorylating and activating the immunosuppressive drug FTY720.

References

Ota, T., et al., Nat. Genet. 36(1):40-45 (2004).
Nava, V.E., et al., FEBS Lett. 473(1):81-84 (2000).
Melendez, A.J., et al., Gene 251(1):19-26 (2000).
Pitson, S.M., et al., Biochem. J. 350 Pt 2, 429-441 (2000).

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